The treatment of Cushing's syndrome was addressed recently by guidelines developed by the Endocrine Society. These indicate that the optimal treatment, when possible, is surgical resection of the causative tumor(s). When this is not possible, or the patient recurs, secondary treatment in Cushing's disease involves radiation therapy with adjunctive use of cortisol-lowering medications, or tumor-directed medical therapy such as cabergoline, or pasireotide or glucocorticoid receptor-directed treatment with mifepristone. Patients with ectopic ACTH secretion may have an occult or widely metastatic tumor, neither of which is amenable to surgical treatment. In this case, medical therapy with cortisol -lowering medications or mifepristone, or bilateral adrenalectomy, may be chosen. Treatments should be individualized to the circumstances, presentation, goals and values of each patient. Co-morbidities should be addressed in addition to primary tumor-directed therapy.